Peracid compositions for medical disinfection

ABSTRACT

A multi-component product for providing, on mixing of the components, a disinfectant composition. A first component of the product comprises an aqueous solution of a lower aliphatic peracid and a second component comprises an aqueous solution containing a corrosion inhibitor and either a hydrogen peroxide stabilizer, a peracid stabilizer, or both.

This invention concerns compositions, processes for the preparation ofsuch compositions, two-pack systems for preparing such compositions anduses of such compositions. More particularly the present inventionconcerns compositions comprising dilute aqueous solutions of loweraliphatic peracids and their use as disinfectant compositions.

The lower aliphatic peracids are effective wide-spectrum bactericideswhich have the particular advantage, in use, of leaving as residues onlythe corresponding lower aliphatic acids and therefore being particularlysuitable for applications which require a non-environmentally-pollutingdisinfectant. While the lower aliphatic peracids in general arecontemplated herein, for example those corresponding to carboxylicaliphatic acids containing 2 to 9 carbon atoms, peracetic acid isparticularly envisaged since it is already a commercially importantperacid for disinfectant purposes. Where the following descriptionrelates to peracetic acid it is to be understood that the other peracidsmay be read in substitution therefor provided that the technical contextallows it.

Aqueous solutions of peracetic acid containing up to about 45 % byweight of peracetic acid are commercially available. Such solutions maybe produced by reacting appropriately concentrated hydrogen peroxide andacetic acid in an aqueous medium in the presence of an acid catalystwhich is usually sulphuric acid or other strong mineral acid. The acidcatalyst may be present in from about 0.1% to about 5% by weight of thereaction mixture.

Aqueous solutions of peracetic acid represent equilibrium mixtures ofthe reactants and the reaction products and, under relatively forcingreaction conditions, for example when using one or more of a substantialquantity of catalyst, an elevated reaction Temperature and aconcentrated reaction mixture, equilibrium may be substantially reachedin a relatively short time. When using the strong acid catalyst in from2% to 5% of the reaction mixture, a temperature of from 30° C. to 50° C.and a concentration of acid above about 20% by weight the reactionmixture may come to equilibrium within hours. For some applications, orwhere long storage is envisaged, it may not be desirable for there to becatalyst residues in a peracid product particularly, for example, diluteproducts intended for personal or domestic hygiene use. For manyapplications dilute solutions of peracetic acid, for example below 5% byweight but often below 2%, for example from 0.1% to 2% by weight, arerequired. Concentrations of peracetic acid above 0.5% by weight forexample from 0.5% to 1% by weight, are particularly effectivebactericidally in, for example, toilet cleansing applications. Suchdilute peracetic acid solutions may be produced directly by reactingacetic acid and hydrogen peroxide in a suitably dilute reaction mediumbut equilibrium can take an extremely long time to reach, particularlyat the more extreme dilutions envisaged. At peracid concentrations below1% by weight equilibrium may take a month or more to reach if thereaction is not acid catalyzed or a week or more even if the reaction isacid catalyzed. This entails a very heavy utilization of plant andequipment on a large production scale.

If a concentrated equilibrium solution of peracetic acid is diluted withwater the equilibrium point of the system is progressively altered, asdilution progresses, in favour of the regeneration of the originalreactants. The ageing time taken to attain the new equilibrium point,after dilution, is of a similar order to that required to produce such adilute solution directly from suitable reactants. Such a dilutedsolution may be used directly although it is not at equilibrium and istherefore of variable composition in storage. Such non-equilibriumdiluted solutions also have a composition dictated by the equilibriumpoint applying at the original concentration, which may not be desiredin some applications. In 1955 Greenspan et al.( Proc. 42nd Ann. Mtg.Chem. Spec. Man. Ass. Dec. 1955), disclosed that stable dilute peraceticacid solutions can be prepared by the use of peracid stabilizers inconjunction with proper adjustment of the relative concentrations of thecomponents of the dilute peracid solution, that is to say that, if theprepared dilute solution is not fully at equilibrium, adjustment of thebalance of the components can achieve stability. The solutions inquestion may be prepared by dilution of commercial, e.g. fullyequilibrated peracetic acid which has been produced by the use of smallamounts of a mineral acid catalyst.

U.S. Pat. No. 4,297,298 describes the production of an aqueous solutionof a lower aliphatic peracid by preparing in a first process step aconcentrated solution of the peracid from the corresponding carboxylicacid or anhydride and concentrated hydrogen peroxide in the presence ofa small quantity of a strong acid catalyst and diluting the solutionwith a solution containing at least one of the reagents from the firstprocess step so as to bring the concentration of the aliphatic peracidto the rated concentration of the mixture the concentration of thediluent reagent or reagents being chosen "so that once dilution has beenbrought about, the system is no longer at equilibrium, but tends to movein the direction of forming further aliphatic peracid at a very slowrate." The process specifically described in U.S. Pat. No. 4,297,298produces a non-equilibrium composition which contains an extremely highconcentration of hydrogen peroxide, e.g. from 28% to 46%. Such aconcentration on contact with the user would cause skin bleaching andpain.

U.S. Pat. No. 4,743,447 describes the production of solutions having ahydrogen peroxide base for disinfecting contact lenses, the solutionhaving from 0.005% to 0.1% by weight of peracetic acid, 1% to 8% byweight of hydrogen peroxide and sufficient acetic acid for the system toreach equilibrium. Such a solution may be prepared by direct reactionusing a very dilute reaction mixture with lengthy equilibration or froma stable commercial solution having a "weak concentration" of peraceticacid to which the other constituents of the composition are added. Thisteaching does not therefore avoid the separate initial step of producinga stable weak solution of peracetic acid from which to produce in turnthe final product.

EP-A-0357238 (Steris Corp) discloses an anti-microbial compositioncomprising a strong oxidant, a copper and brass corrosion inhibitor, abuffering agent, at least one anti-corrosive agent which exhibitscorrosion inhibition in at least aluminium, carbon steel and stainlesssteel, and a wetting agent. The corrosion inhibitors specificallydisclosed for brass and aluminium comprise triazoles and molybdates,which are known to have unfavourable toxicity, and which thereforerenders undesirable their use in a medical environment.

It is an object of the present invention to provide a disinfectantcomposition, based on a dilute solution of peracid, which may be used onmedical equipment comprising metal components to be disinfected.

In accordance with the present invention there is provided a process forthe preparation of an aqueous disinfectant composition characterized inthat the process comprises mixing a first aqueous solution comprising alower aliphatic peracid with a second aqueous solution comprising acorrosion inhibitor and a hydrogen peroxide stabilizer and/or peracidstabilizer.

In another aspect, the present invention provides a disinfectantcomposition obtainable by a process comprising mixing a first aqueoussolution comprising a lower aliphatic peracid with a second aqueoussolution comprising a corrosion inhibitor and a hydrogen peroxidestabilizer and/or peracid stabilizer. It is to be understood that theperacid composition of the present invention is not in equilibrium andcomprises a relatively higher concentration of stabilizer(s) than askilled person would expect to find in a composition which is inequilibrium and comprises a similar concentration of peracid

In yet another aspect, the present invention provides a two-pack systemfor the preparation of a disinfectant composition, characterised in thatone pack comprises a first aqueous solution comprising a lower aliphaticperacid, and the other pack comprises a second aqueous solutioncomprising a corrosion inhibitor and a hydrogen peroxide stabilizerand/or peracid stabilizer.

The first aqueous solution preferably comprises a lower aliphaticperacid, such as peracetic acid, in an amount of from 2% to 10%, morepreferably from 3% to 7%, by weight of the solution. The first aqueoussolution may additionally comprise stabilizer(s) for the hydrogenperoxide and/or the peracid in the equilibrium solution, each relevantstabilizer being present in a preferred amount of from 20 to 10,000 ppm.Preferably both the peroxide and peracid are stabilized in the solution,giving a preferred combined stabilizer concentration of from 3000 to6000 ppm. A suitable peracid stabilizer is dipicolinic acid and suitableperoxide stabilizers include phosphonic acids and salts thereof, e.g.the products sold by Monsanto under the trade mark "DEQUEST" such ashydroxyethylidenediphosphonate, diethylenetriaminepentamethylenephosphonate and ethylenediaminetetramethylene phosphonate and thosestabilizers claimed in European patent application 0426949, especiallycyclohexane-1,2-diaminotetramethylenephosphonic acid and salts thereof(CDTMP). It should be understood that the first solution is usually anequilibrium mixture of the relevant reactants and reaction products, asgenerally described in the paragraph bridging page 1 and page 2 above,and that the above specified amount of peracid indicates the amount ofperacid per se in the solution. A preferred process for the preparationof dilute solutions of lower aliphatic peracids useful in the presentinvention is disclosed in PCT Patent Application No. WO 91/13058.

The second aqueous solution preferably comprises from 0.1% to 5%, morepreferably from 0.1% to 1%, by weight of the solution of a corrosioninhibitor. Preferably, the corrosion inhibitor is an alkali metalphosphate, most preferably a potassium phosphate. Dipotassium hydrogenorthophosphate (K₂ HPO₄) is the most preferred corrosion inhibitor.

The second aqueous solution preferably comprises from 0.1% to 2%, often0.1% to 1%, more preferably from 0.2% to 0.7% or 0.7% to 1%, by weightof the solution of hydrogen peroxide stabilizer and/or peracidstabilizer, such as about 0.5% or about 1% stabilizer. Preferably ahydrogen peroxide stabilizer is used, The preferred peroxide stabilizersare phosphonic acids and salts thereof, for example, those describedhereinabove as suitable for the first aqueous solution. A suitableperacid stabilizer is dipicolinic acid.

Mixing of the first and second solutions give a disinfectant compositionimmediately after mixing comprising at least 0.05% and generally notgreater than 1% by weight peracid. In many embodiments, the mixture ofthe two solutions immediately after mixing comprises from 0.1% to 0.25%or from 0.25% to 0.5% by weight peracid. The mixture also desirablycomprises from 0.1% to 5% corrosion inhibitor and from 0.1% to 1%peroxide stabilizer and/or peracid stabilizer. Such mixtures can oftenbe obtained conveniently by selecting a volume ratio of the firstsolution to the second solution which is often at least 1:5 and notusually greater than 1:50, preferably from 1:10 to 1:30, taking intoaccount the concentration of the components in each solution.

One or both of the aqueous solutions may contain other components usefulin disinfectant compositions, e.g. a triazole corrosion inhibitor and/ora wetting agent, though the presence of these components is notessential to obtain the advantages of the invention (indeed, suchcomponents may be slightly detrimental). One or both of the solutionsmay contain an indicator which undergoes a colour change to indicatethat the two solutions have been mixed together.

It will be appreciated that the compositions provided by the process ofthe present invention are not in equilibrium and that in the naturalcourse of events the peracid component of the composition will tendtowards equilibrium. For example, the composition described in theparagraph immediately above this paragraph will begin to change within arelatively short period of time from mixing the first and secondsolutions together and that as time passes the peracid concentration inthe solution will reduce as it tends towards equilibrium. Normalequilibrium could be expected to be reached after about two days,assuming the peracid and/or peroxide does not decompose in that period.

The compositions of the present invention are particularly suitable foruse as medical disinfectants. Preferably, the compositions are used todisinfect medical equipment which has metal, e.g. aluminium, brass,copper and especially steel, components required to be disinfected. Forexample, the composition is particularly useful for disinfection ofendoscopes. The present invention may have a further advantage over theprior art compositions of Steris. The selected components of theinvention composition interact to protect metal components, especiallysteel components, with regard to localized corrosion, e.g. pitting, aswell as, if not better than, if molybdate, triazole and/or wetting agentwere present. This is most surprising in light of the disclosure on page4, lines 7 to 9, of Steris.

The present invention has the advantage of providing a dilutecomposition comprising a relatively high concentration of peracid.Furthermore, the process of the present invention enables a relativelylonger shelf life for the separate aqueous solution than would beachieved if the composition was supplied per se.

The invention will now be further described, without limitation, withreference to the following examples:

EXAMPLE 1

Preparation of Composition according to the Present Invention

A two-pack system was prepared. One pack contained 250 ml of an aqueousperacetic acid, 5% (active) by weight, solution. The other packcontained 10 l of an aqueous solution comprising 0.6% by weightdipotassium hydrogen ortho phosphate and 0.5% by weight CDTMP. The twopacks were then mixed together to form a composition of the presentinvention.

EXAMPLE 2

Preparation of Composition according to the Present Invention

A solution of 5% w/w peracetic acid, 20% w/w hydrogen peroxide, 8% w/wacetic acid was diluted 14 times with a solution containing 1% w/w CDTMPand 0.8% dipotassium hydrogen orthophosphate to form a solutioncontaining 3,500 ppm peracetic acid.

EXAMPLE 3 AND COMPARISON A

Corrosion Trials for Disinfectant Compositions

Duplicate coupons of mild steel and stainless steel 316 were immersedfor 72 hours at room temperature (15°-25° C.) in disinfectant solutions.In Example 3, the disinfectant solution was prepared according to themethod of Example 2 after a dilution by 25 times to produce a solutioncontaining 2000 ppm peracetic acid. In Comparison A, the disinfectantsolution was prepared according to the example given in the first table,page 6, lines 1 to 18 of European Patent Application No 0 357 238. Thesolutions were completely replaced daily with fresh solutions.Examination of the coupons with both the naked eye and an opticalmicroscope on completion of the trial showed that for both of the metalsin the composition according to the Steris Application, there wassignificant localized corrosion and pitting on the metal but for themetals in the disinfectant solution according to the present inventionthere was only very slight localised corrosion.

The significant reduction in localized corrosion achieved withcompositions according to the present invention is surprising given thedisclosure on page 4, lines 7 to 9 of the Steris Application, and isparticularly advantageous because the results were achieved without theuse of any toxic molybdate and triazole.

We claim:
 1. A process for the preparation of an aqueous disinfectantcomposition comprising mixing a first aqueous solution comprising alower aliphatic peracid with a second aqueous solution comprising aphosphate corrosion inhibitor and at least one hydrogen peroxidestabilizer selected from the group consisting of phosphonic acids andsalts thereof.
 2. A process as claimed in claim 1, wherein the firstaqueous solution comprises a (C₂ -C₉) aliphatic peracid in an amount offrom 2% to 10% by weight of the first aqueous solution.
 3. A process asclaimed in claim 1, wherein the first aqueous solution comprises a (C₂-C₉) aliphatic peracid in an amount of from 3% to 7% by weight of thefirst aqueous solution.
 4. A process as claimed in claim 2 or 3, whereinthe aliphatic peracid comprises peracetic acid.
 5. A process as claimedin claim 1, 2 or 3 wherein the second aqueous solution comprises from0.1% to 5% by weight of the second aqueous solution of the phosphatecorrosion inhibitor.
 6. A process as claimed in claim 5, wherein thesecond aqueous solution comprises from 0.1% to 1% by weight of thesecond aqueous solution of the phosphate corrosion inhibitor.
 7. Aprocess as claimed in claim 5, wherein the phosphate corrosion inhibitorcomprises an alkali metal phosphate.
 8. A process as claimed in claim 6wherein the phosphate corrosion inhibitor comprises dipotassium hydrogenorthophosphate.
 9. A process as claimed in claim 1 wherein the secondaqueous solution comprises from 0.1% to 2% by weight of the secondaqueous solution of said at least one hydrogen peroxide stabilizer. 10.A process as claimed in claim 9 wherein the second aqueous solutioncomprises from 0.2% to 1% by weight of the second aqueous solution ofsaid at least one hydrogen peroxide stabilizer.
 11. A process as claimedin claim 1 wherein said hydrogen peroxide stabilizer comprisescyclohexane-1, 2-diaminotetramethylenephosphonic acid or salt thereof.12. A process as claimed in claim 1, 2, 3, 9 or 10, wherein the ratio ofthe volume of the first aqueous solution to the volume of the secondaqueous solution is 1:5 to 1:50.
 13. A process as claimed in claim 12wherein the ratio of the volume of the first aqueous solution to thevolume of the second aqueous solution is 1:10 to 1:30.
 14. A process asclaimed in claim 1, 2, 3, 9 or 10, wherein at least one of the first andsecond aqueous solutions comprises an indicator which undergoes a colourchange when the solutions are mixed together.
 15. A process according toany one of claims 1, 2, 3, 9 or 10, wherein said phosphate corrosioninhibitor comprises a steel corrosion inhibitor.
 16. A multi-componentproduct for providing, on mixing of the components, a disinfectantcomposition, said product comprising a first component which comprises afirst aqueous solution comprising a lower aliphatic peracid, and asecond component which comprises a second aqueous solution comprising aphosphate corrosion inhibitor and at least one hydrogen peroxidestabilizer selected from the group consisting of phosphonic acids andsalts thereof.
 17. A multi-component product as claimed in claim 16,wherein the first aqueous solution comprises a (C₂ -C₉) aliphaticperacid in an amount of from 2% to 10% by weight of the first aqueoussolution.
 18. A multi-component product as claimed in claim 16, whereinthe first aqueous solution comprises a (C₂ -C₉) aliphatic peracid in anamount of from 3% to 7% by weight of the first aqueous solution.
 19. Amulti-component product as claimed in claim 17 or 18, wherein thealiphatic peracid comprises peracetic acid.
 20. A multi-componentproduct as claimed in claim 16, 17 or 18 wherein the second aqueoussolution comprises from 0.1% to 5% by weight of the second aqueoussolution of the phosphate corrosion inhibitor.
 21. A multi-componentproduct as claimed in claim 20, wherein the second aqueous solutioncomprises from 0.1% to 1% by weight of the second aqueous solution ofthe phosphate corrosion inhibitor.
 22. A multi-component product asclaimed in claim 20, wherein the phosphate corrosion inhibitor comprisesan alkali metal phosphate.
 23. A multi-component product as claimed inclaim 21 wherein the phosphate corrosion inhibitor comprises dipotassiumhydrogen orthophosphate.
 24. A multi-component product as claimed inclaim 16 wherein the second aqueous solution comprises from 0.1% to 2%by weight of the second aqueous solution of said at least one hydrogenperoxide stabilizer.
 25. A multi-component product as claimed in claim28 wherein the second aqueous solution comprises from 0.2% to 1% byweight of the second aqueous solution of said at least one hydrogenperoxide stabilizer.
 26. A multi-component product as claimed in claim16 wherein said hydrogen peroxide stabilizer comprises cyclohexane-1,2-diaminotetramethylenephosphonic acid or salt thereof.
 27. Amulti-component product as claimed in claim 16, 17, 18, 24 or 25,wherein the ratio of the volume of the first aqueous solution to thevolume of the second aqueous solution is 1:5 to 1:50.
 28. Amulti-component product as claimed in claim 27 wherein the ratio of thevolume of the first aqueous solution to the volume of the second aqueoussolution is 1:10 to 1:30.
 29. A multi-component product as claimed inclaim 16, 17, 18, 24 or 25, wherein at least one of the first and secondaqueous solutions comprises an indicator which undergoes a colour changewhen the solutions are mixed together.
 30. A multi-component productaccording to any one of claims 16, 17, 18, 24 or 25, wherein saidphosphate corrosion inhibitor comprises a steel corrosion inhibitor.